Burden and Risk of Neurological and Cognitive Impairment in Pediatric Sickle Cell Anemia in Uganda Sickle Cell Anemia (SCA) is the most common inherited disorder in sub-Saharan Africa. In Uganda, an estimated 20,000 children are born with SCA annually. Vasculopathy in SCA is associated with brain injury and affect neurologic and cognitive function. Brain injury in pediatric SCA may follow acute inflammatory events, including infections. Acute bacterial, malarial and other infections and malnutrition are highly prevalent in SSA, and may contribute to or precipitate SCA vascular brain injury. Our goal is to establish the burden and clinical spectrum of pediatric brain injury from SCA, identify risk factors, and build research capacity to support interventions for brain injury reduction. Our hypothesis is that risk factors (sickle vasculopathy, malnutrition, other) independently or with triggers (inflammation or infections) predispose children with SCA in SSA to a high burden of neurological and cognitive impairments. The objectives of this application are to determine the age-related spectrum and burden of brain injury associated with SCA in Ugandan children, and determine the predisposing risk factors. Knowledge of the magnitude of brain injury from SCA and the underlying risk factors will drive the design of future studies on pathogenesis and preventive measures to improve outcome. In response to PAR-14-331, we propose to: Aim 1. Determine the burden and spectrum of neurological and cognitive impairment in children with SCA aged 0-12 years in Uganda; Aim 2. Examine risk factors or triggers for neurological and cognitive impairment in children with SCA in the same sample; and Aims 3. Enhance existing brain research capacity in Uganda through the study of pediatric neurologic and cognitive impairment in SCA. Through this work, we will have established an estimate of the burden, spectrum and associated risk factors and triggers for brain injury in children with SCA in Uganda, a SCA repository; developed a cohort to follow prospectively; inform the design of prospective studies to understand the pathogenesis and test interventions to reduce the burden of brain injury in SCA in Uganda; and increased capacity for carrying out north-south and south-south research collaborations in SCA and will fill a substantial gap in our institutional, national and regional capacity in brain research and training across the lifespan.